Various agents have been applied topically to treat infected wounds for millennia, but their proper role remains unclear. Topical therapy affords many potential advantages but also has disadvantages. Opinions differ on which clinical signs define wound infection and on whether quantitative microbiological studies are useful. Clinically infected wounds usually require systemic antibiotic therapy, whereas clinically uninfected wounds that are healing as expected do not require antimicrobials. There is controversy over how to treat poorly healing wounds with "secondary" signs suggesting infection; these may benefit from topical antimicrobial agents. Some evidence supports using topical agents for malodorous or burn wounds. Meta-analyses and systematic reviews suggest there are few proven indications for topical antimicrobials. Use of a newer, relatively nontoxic antiseptic (eg, cadexomer iodine or silver dressings) is preferable to use of topical antibiotics, especially agents that are available for systemic use. We provide clinically relevant information on currently available topical antimicrobial agents.